scholarly journals Expression Pattern of T-Type Ca2+ Channels in Cerebellar Purkinje Cells after VEGF Treatment

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2277
Author(s):  
Jonas Tjaden ◽  
Annika Eickhoff ◽  
Sarah Stahlke ◽  
Julian Gehmeyr ◽  
Matthias Vorgerd ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Calcium Influx ◽  
Vegf Receptor ◽  
Channel Expression ◽  
The Central Nervous System ◽  
Cerebellar Purkinje Cells ◽  
The Impact ◽  
Ca2 Channels

T-type Ca2+ channels, generating low threshold calcium influx in neurons, play a crucial role in the function of neuronal networks and their plasticity. To further investigate their role in the complex field of research in plasticity of neurons on a molecular level, this study aimed to analyse the impact of the vascular endothelial growth factor (VEGF) on these channels. VEGF, known as a player in vasculogenesis, also shows potent influence in the central nervous system, where it elicits neuronal growth. To investigate the influence of VEGF on the three T-type Ca2+ channel isoforms, Cav3.1 (encoded by Cacna1g), Cav3.2 (encoded by Cacna1h), and Cav3.3 (encoded by Cacna1i), lasermicrodissection of in vivo-grown Purkinje cells (PCs) was performed, gene expression was analysed via qPCR and compared to in vitro-grown PCs. We investigated the VEGF receptor composition of in vivo- and in vitro-grown PCs and underlined the importance of VEGF receptor 2 for PCs. Furthermore, we performed immunostaining of T-type Ca2+ channels with in vivo- and in vitro-grown PCs and showed the distribution of T-type Ca2+ channel expression during PC development. Overall, our findings provide the first evidence that the mRNA expression of Cav3.1, Cav3.2, and Cav3.3 increases due to VEGF stimulation, which indicates an impact of VEGF on neuronal plasticity.

scholarly journals A sand fly salivary protein acts as a neutrophil chemoattractant

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anderson B. Guimaraes-Costa ◽  
John P. Shannon ◽  
Ingrid Waclawiak ◽  
Jullyanna Oliveira ◽  
Claudio Meneses ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Calcium Influx ◽  
Parasite Burden ◽  
Salivary Protein ◽  
Sand Fly ◽  
Human Neutrophils ◽  
Chemotactic Protein ◽  
The Impact

AbstractApart from bacterial formyl peptides or viral chemokine mimicry, a non-vertebrate or insect protein that directly attracts mammalian innate cells such as neutrophils has not been molecularly characterized. Here, we show that members of sand fly yellow salivary proteins induce in vitro chemotaxis of mouse, canine and human neutrophils in transwell migration or EZ-TAXIScan assays. We demonstrate murine neutrophil recruitment in vivo using flow cytometry and two-photon intravital microscopy in Lysozyme-M-eGFP transgenic mice. We establish that the structure of this ~ 45 kDa neutrophil chemotactic protein does not resemble that of known chemokines. This chemoattractant acts through a G-protein-coupled receptor and is dependent on calcium influx. Of significance, this chemoattractant protein enhances lesion pathology (P < 0.0001) and increases parasite burden (P < 0.001) in mice upon co-injection with Leishmania parasites, underlining the impact of the sand fly salivary yellow proteins on disease outcome. These findings show that some arthropod vector-derived factors, such as this chemotactic salivary protein, activate rather than inhibit the host innate immune response, and that pathogens take advantage of these inflammatory responses to establish in the host.

scholarly journals Adverse Effects of Methylene Blue on the Central Nervous System

2008 ◽  
Vol 108 (4) ◽  
pp. 684-692 ◽  
Author(s):  
Laszlo Vutskits ◽  
Adrian Briner ◽  
Paul Klauser ◽  
Eduardo Gascon ◽  
Alexandre G. Dayer ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Cell Death ◽  
Neuronal Cultures ◽  
Dendritic Arbor ◽  
Field Potentials ◽  
Neurotoxic Effects ◽  
The Central Nervous System ◽  
The Impact

Background An increasing number of clinical observations suggest adverse neurologic outcome after methylene blue (MB) infusion in the setting of parathyroid surgery. Hence, the aim of the current study was to investigate the potentially neurotoxic effects of MB using a combination of in vivo and in vitro experimental approaches. Methods Isoflurane-anesthetized adult rats were used to evaluate the impact of a single bolus intravascular administration of MB on systemic hemodynamic responses and on the minimum alveolar concentration (MAC) of isoflurane using the tail clamp test. In vivo, MB-induced cell death was evaluated 24 h after MB administration using Fluoro-Jade B staining and activated caspase-3 immunohistochemistry. In vitro, neurotoxic effects of MB were examined in hippocampal slice cultures by measuring excitatory field potentials as well as propidium iodide incorporation after MB exposure. The impact of MB on dendritic arbor was evaluated in differentiated single cell neuronal cultures. Results Bolus injections of MB significantly reduced isoflurane MAC and initiated widespread neuronal apoptosis. Electrophysiologic recordings in hippocampal slices revealed a rapid suppression of evoked excitatory field potentials by MB, and this was associated with a dose-dependent effect of this drug on cell death. Dose-response experiments in single cell neuronal cultures revealed that a 2-h-long exposure to MB at non-cell-death-inducing concentrations could still induce significant retraction of dendritic arbor. Conclusions These results suggest that MB exerts neurotoxic effects on the central nervous system and raise questions regarding the safety of using this drug at high doses during parathyroid gland surgery.

Development of inositol 1,4,5-triphosphate 3-kinase immunoreactivity in cerebellar Purkinje cells in vivo and in vitro

1992 ◽  
Vol 573 (1) ◽  
pp. 157-160 ◽  
Author(s):  
Masashi Mizuguchi ◽  
Mitsunori Yamada ◽  
Sue Goo Rhee ◽  
Seung U. Kim
Keyword(s):  
Purkinje Cells ◽  
Cerebellar Purkinje Cells

scholarly journals Cbln1 Regulates Rapid Formation and Maintenance of Excitatory Synapses in Mature Cerebellar Purkinje Cells In Vitro and In Vivo

2008 ◽  
Vol 28 (23) ◽  
pp. 5920-5930 ◽  
Author(s):  
A. Ito-Ishida ◽  
E. Miura ◽  
K. Emi ◽  
K. Matsuda ◽  
T. Iijima ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Excitatory Synapses ◽  
Rapid Formation ◽  
Cerebellar Purkinje Cells

scholarly journals Human Cerebrospinal Fluid Modulates Pathways Promoting Glioblastoma Malignancy

2021 ◽  
Vol 11 ◽  
Author(s):  
Anna Carrano ◽  
Natanael Zarco ◽  
Jordan Phillipps ◽  
Montserrat Lara-Velazquez ◽  
Paola Suarez-Meade ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebrospinal Fluid ◽  
Expression Patterns ◽  
Therapeutic Implications ◽  
Transcriptional Changes ◽  
The Central Nervous System ◽  
And Migration ◽  
The Impact

Glioblastoma (GBM) is the most common and devastating primary cancer of the central nervous system in adults. High grade gliomas are able to modify and respond to the brain microenvironment. When GBM tumors infiltrate the Subventricular zone (SVZ) they have a more aggressive clinical presentation than SVZ-distal tumors. We suggest that cerebrospinal fluid (CSF) contact contributes to enhance GBM malignant characteristics in these tumors. We evaluated the impact of human CSF on GBM, performing a transcriptome analysis on human primary GBM cells exposed to CSF to measure changes in gene expression profile and their clinical relevance on disease outcome. In addition we evaluated the proliferation and migration changes of CSF-exposed GBM cells in vitro and in vivo. CSF induced transcriptomic changes in pathways promoting cell malignancy, such as apoptosis, survival, cell motility, angiogenesis, inflammation, and glucose metabolism. A genetic signature extracted from the identified transcriptional changes in response to CSF proved to be predictive of GBM patient survival using the TCGA database. Furthermore, CSF induced an increase in viability, proliferation rate, and self-renewing capacity, as well as the migratory capabilities of GBM cells in vitro. In vivo, GBM cells co-injected with human CSF generated larger and more proliferative tumors compared to controls. Taken together, these results provide direct evidence that CSF is a key player in determining tumor growth and invasion through the activation of complex gene expression patterns characteristic of a malignant phenotype. These findings have diagnostic and therapeutic implications for GBM patients. The changes induced by CSF contact might play a role in the increased malignancy of SVZ-proximal GBM.

On the DNA content of cerebellar Purkinje cells in vivo and in vitro

1974 ◽  
Vol 43 (1) ◽  
pp. 192-206 ◽  
Author(s):  
Laura Manuelidis ◽  
Elias E. Manuelidis
Keyword(s):  
Purkinje Cells ◽  
Dna Content ◽  
Cerebellar Purkinje Cells

scholarly journals Toxicity of metallic nanoparticles in the central nervous system

2019 ◽  
Vol 8 (1) ◽  
pp. 175-200 ◽  
Author(s):  
Krzysztof Sawicki ◽  
Magdalena Czajka ◽  
Magdalena Matysiak-Kucharek ◽  
Berta Fal ◽  
Bartłomiej Drop ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Metallic Nanoparticles ◽  
Current Knowledge ◽  
Negative Effects ◽  
Scientific Publications ◽  
The Central Nervous System ◽  
The Impact

Abstract Metallic nanoparticles due to their small size and unique physico-chemical characteristics have found excellent applications in various branches of industry and medicine. Therefore, for many years a growing interest has been observed among the scientific community in the improvement of our understanding of the impact of nanoparticles on the living organisms, especially on humans. Considering the delicate structure of the central nervous systemit is one of the organs most vulnerable to the adverse effects of metallic nanoparticles. For that reason, it is important to identify the modes of exposure and understand the mechanisms of the effect of nanoparticles on neuronal tissue. In this review, an attempt is undertaken to present current knowledge about metallic nanoparticles neurotoxicity based on the selected scientific publications. The route of entry of nanoparticles is described, as well as their distribution, penetration through the cell membrane and the blood-brain barrier. In addition, a study on the neurotoxicity in vitro and in vivo is presented, as well as some of the mechanisms that may be responsible for the negative effects of metallic nanoparticles on the central nervous system. Graphical abstract: This review summarizes the current knowledge on the toxicity of metallic NPs in the brain and central nervous system of the higher vertebrates.

scholarly journals Disrupting the leukemia niche in the central nervous system attenuates leukemia chemoresistance

2019 ◽  
Author(s):  
Leslie M. Jonart ◽  
Maryam Ebadi ◽  
Patrick Basile ◽  
Kimberly Johnson ◽  
Jessica Makori ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cells ◽  
Adhesion Assay ◽  
Hematopoietic Stem ◽  
The Central Nervous System ◽  
The Impact

AbstractProtection from acute lymphoblastic leukemia (ALL) relapse in the central nervous system (CNS) is crucial to survival and quality of life for ALL patients. Current CNS-directed therapies cause significant toxicities and are only partially effective. Moreover, the impact of the CNS microenvironment on leukemia biology is poorly understood. Herein, we showed that leukemia cells associated with the meninges of xenotransplanted mice, or co-cultured with meningeal cells, exhibit enhanced chemoresistance due to effects on both apoptosis balance and quiescence. From a mechanistic standpoint, we identified that leukemia chemoresistance is primarily mediated by direct leukemia-meningeal cell interactions and overcome by detaching the leukemia cells from the meninges. Next, we used a co-culture adhesion assay to identify drugs that disrupted leukemia-meningeal adhesion. In addition to identifying several drugs that inhibit canonical cell adhesion targets we found that Me6TREN, a novel hematopoietic stem cell (HSC) mobilizing compound, also disrupts leukemia-meningeal adhesion in vitro and in vivo. Finally, Me6TREN enhanced the efficacy of cytarabine in treating CNS leukemia in xenotransplanted mice. This work demonstrates that the meninges exert a critical influence on leukemia chemoresistance, elucidates mechanisms of CNS relapse beyond the well-described role of the blood-brain barrier, and identifies novel therapeutic approaches for overcoming chemoresistance.

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